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Extracellular Vesicles are nanometer sized (40-5000 nm diameter) particles endogenously released by cells in a constitutive or inducible manner [1-3]. Extracellular Vesicles are found in every body fluids. They contain membrane proteins and lipids as well as other cytoplasmic components. Their composition depends on the parental cell.

Extracellular Vesicles are composed of three major classes : 

- Exosomes (30 - 100 nm) originating from multi vesicular bodies (MVB).

- Microvesicles (100-500 nm) directly bud from the plasma membrane.

- Apoptotic bodies (500 nm - 5 µm) are a population of extracellular vesicles secreted during cell death by apoptosis. 

Extracellular Vesicles

Exosomes

Microvesicles

Cell

Apoptotic bodies

Exosomes are originating from multi vesicular bodies (MVB) that are intracellular organelles belonging to the endosomal pathway. After the fusion of the MVB with the plasma membrane, the cargo containing exosomes is released in the extracellular environment. Exosomes are enriched in tetraspanins such as CD9, CD63, CD81 (membrane proteins), endosomes and membrane binding proteins such as RAB (RAB11A, RAB5B and RAB11B), annexins and TSG101.

MVB

Microvesicles are directly bud from the plasma membrane. Microvesicles are enriched in intracellular proteins such as HSP90B1, CANX, GM130. Other markers such as CD63, CD81, CD9, RAB11A, RAB5B and annexins are also presents in microvesicles. 

Apoptotic bodies are released during cell death by apoptosis. During this physiological process, the cell released a large fraction of its intracellular components in the apoptotic bodies.  Apoptotic bodies contain most of the cell content and contrary to other extracellular vesicles, they contain small portions of 180 base pairs of DNA.

There are no specific markers that distinguish the sub-categories of exosomes and microvesicles from each other. In a position paper [1] the International Society for Extracellular Vesicles (ISEV) proposes to define the extracellular vesicles subset enrichment by three categories of proteins :

- Transmembrane or lipid-bound extracellular proteins that are present or enriched in exosomes (such as tetraspanins, integrins..)

- Cytosolic proteins that are present or enriched in exosomes (such as TSG101, RAB, ANXA..)

- Intracellular proteins that are absent or under-represented in exosomes but present in other type of extracellular vesicles (such as the endoplasmic reticulum, the Golgi apparatus, the mitochondrial, the nucleus..). 

[1] : Journal of Extracellular Vesicles, 2014, 3, 26913.